Hexosaminidase A deficiency in adults

Area of Science:

• Biochemistry
• Genetics
• Neurology

Background:

• Hexosaminidase A (Hex A) deficiency in adults is a rare condition.
• Previous studies on adult Hex A deficiency have reported varied clinical presentations and biochemical findings.

Purpose of the Study:

• To report clinical, biochemical, and genetic findings in 15 individuals with adult Hex A deficiency from nine Ashkenazi families.
• To compare these findings with previously reported cases.
• To investigate the molecular basis of Hex A deficiency in affected individuals.

Main Methods:

• Clinical assessment of neurological symptoms and family history.
• Biochemical assays of Hex A activity in serum, leukocytes, and fibroblasts.
• Analysis of Hex A alpha and beta chain precursor synthesis in cultured skin fibroblasts.

Main Results:

• Fifteen individuals from nine families were identified; 14 had neurological symptoms, and one was asymptomatic.
• Clinical phenotypes varied, including spinocerebellar, motor neuron, and cerebellar syndromes, with psychosis in 30% of cases.
• Biochemical analysis showed Hex A activity in the Tay-Sachs disease (TSD) range, with some residual activity detected by sensitive methods. Fibroblast studies revealed reduced alpha chain precursor synthesis and absence of mature Hex A chains.

Conclusions:

• Adult Hex A deficiency exhibits significant clinical variability, making phenotype-based genetic classification challenging.
• Residual Hex A activity and altered precursor synthesis in fibroblasts indicate a complex molecular pathology.
• Further research is needed to fully elucidate the genotype-phenotype correlations and disease mechanisms in adult Hex A deficiency.